title: Liposome formulation of co-encapsulated vincristine and quercetin enhanced antitumor activity in a trastuzumab-insensitive breast tumor xenograft model.
abstract: Hormone- and trastuzumab-insensitive breast cancer has limited and ineffective clinical treatment options. This study sought to develop a liposome formulation containing a synergistic combination of vincristine and quercetin, with prolonged drug circulation times and coordinated drug release in vivo, to develop effective treatments against this subtype of breast cancer. The 2:1 molar ratio of vincristine/quercetin showed strong synergism in the hormone- and trastuzumab-insensitive JIMT-1 cells. Liposome co-encapsulation prolonged plasma circulation of the two drugs and maintained the synergistic drug ratio in vivo. Furthermore, the co-encapsulated liposome formulation demonstrated the most effective tumor growth inhibition in the JIMT-1 human breast tumor xenograft in comparison with vehicle control, free quercetin, free vincristine and free vincristine/quercetin combinations. Specifically, only the co-encapsulated liposome formulation exhibited significant antitumor activity at two-thirds of the maximum tolerated dose of vincristine, without significant body weight loss in the animals.
  
  
  BACKGROUND
  In this study, a novel liposome formulation containing a synergistic combination of vincristine and quercetin was utilized in the treatment of breast cancer. Prolonged drug circulation times and coordinated drug release characterize this effective treatment, which may find its way to clinical applications in the near future.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Man-Yi
authors.initials: MY
authors.lastname: Wong
authors.forename: Gigi N C
authors.initials: GN
authors.lastname: Chiu
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D016513:Mice, SCID; D011794:Quercetin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000068878:Trastuzumab; D014750:Vincristine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008081:Liposomes; D014750:Vincristine; D011794:Quercetin; D000068878:Trastuzumab